CD40 receptor (Tumor necrosis factor receptor superfamily member 5) (CD40)

CD40 (Tumor Necrosis Factor Receptor Superfamily Member 5) is a 48 kDa type I transmembrane glycoprotein primarily expressed on antigen-presenting cells (APCs) such as B cells, dendritic cells, and macrophages (UniProt P25942). It plays a pivotal role in the adaptive immune system by interacting with its ligand, CD40L (CD154), which is transiently expressed on activated T helper cells (PubMed: 29109432). This interaction is fundamental for B-cell differentiation, immunoglobulin class switching from IgM to IgG, IgA, and IgE, and the formation of long-lived memory B cells (StatPearls: NBK531486). In patients with X-linked Hyper-IgM Syndrome (HIGM1), the CD40LG gene is defective, leading to a failure of this signaling axis and resulting in severe immunodeficiency characterized by low levels of serum IgG and IgA (NIH: Genetic and Rare Diseases Information Center). Recent therapeutic advances utilize CRISPR/Cas9 or viral vectors to restore functional CD40L expression on T cells or hematopoietic stem and progenitor cells (HSPCs), thereby re-enabling the activation of the CD40 receptor on endogenous APCs (PubMed: 32661335). Additionally, CD40 is a prominent target in oncology, where agonistic antibodies are employed to "license" dendritic cells and promote a robust cytotoxic T-cell response against tumors (PubMed: 30633910).

Other names

TNFRSF5B-cell surface antigen CD40Bp50CDW40Tumor necrosis factor receptor superfamily member 5

Agonism of the CD40 receptor, either via monoclonal antibodies or restored expression of CD40 ligand (CD154), to trigger intracellular signaling pathways (e.g., NF-kappaB, MAPK) that activate antigen-presenting cells and enhance T-cell mediated immunity.